Methods of whitening teeth

ABSTRACT

The present invention relates to improved dental compositions and methods for bleaching teeth. More specifically, this invention is directed towards hydrogen peroxide-containing compounds that are maintained at a substantially constant pH range of 6.0-10.0 during the tooth-bleaching procedure in the presence of a calcium chelating agent.

RELATED U.S. APPLICATION(S)

[0001] The present application is a continuation of U.S. applicationSer. No. 09/192,609, filed on Nov. 16, 1998, itself a divisional of U.S.application Ser. No. 08/719,569, filed on Sep. 25, 1996, which issued onJul. 13, 1999 as U.S. Pat. No. 5,922,307, and which claims priority fromProvisional Application Serial No. 60/004,258, filed Sep. 25, 1995, allof which are hereby incorporated herein by reference.

TECHNICAL FIELD

[0002] The present invention relates to improved dental bleachingcompositions and methods for bleaching teeth.

BACKGROUND ART

[0003] White teeth have long been considered cosmetically desirable.Unfortunately, teeth become almost invariably discolored in the absenceof intervention. The tooth structures which are generally responsiblefor presenting a stained appearance are enamel, dentin, and the acquiredpellicle. Tooth enamel is predominantly formed from inorganic material,mostly in the form of hydroxyapatite crystals and further containsapproximately 5% organic material primarily in the form of collagen. Incontrast, dentin is composed of about 20% protein including collagen,the balance consisting of inorganic material, predominantlyhydroxyapatite crystals, similar to that found in enamel. The acquiredpellicle is a proteinaceous layer on the surface of tooth enamel whichreforms rapidly after an intensive tooth cleaning.

[0004] Staining of teeth results from extrinsic and/or intrinsicstaining. Extrinsic staining of the acquired pellicle arises as a resultof compounds such as tannins and polyphenolic compounds which becometrapped in and tightly bound to the proteinaceous layer on the surfaceof the teeth. This type of staining can usually be removed by mechanicalmethods of tooth cleaning. In contrast, intrinsic staining occurs whenstaining compounds penetrate the enamel and even the dentin or arisefrom sources within the tooth. This type of staining is not amenable tomechanical methods of tooth cleaning and chemical methods are required.

[0005] Consequently, tooth-bleaching compositions generally fall intotwo categories: (1) gels, pastes, or liquids, including toothpastes thatare mechanically agitated at the stained tooth surface in order toaffect tooth stain removal through abrasive erosion of stained acquiredpellicle; and (2) gels, pastes, or liquids that accomplish thetooth-bleaching effect by a chemical process while in contact with thestained tooth surface for a specified period, after which theformulation is removed. In some cases, the mechanical process issupplemented by an auxiliary chemical process which may be oxidative orenzymatic.

[0006] The majority of professionally-monitored at-home tooth-bleachingcompositions act by oxidation. These compositions are dispensed directlyto a patient for use in a custom-made tooth-bleaching tray, held inplace in the mouth for contact times of greater than about 60 minutes,and sometimes as long as 8 to 12 hours. The slow rate of bleaching is inlarge part, the consequence of formulations that are developed tomaintain stability of the oxidizing composition. The most commonly usedoxidative compositions contain the hydrogen peroxide precursor carbamideperoxide which is mixed with an anhydrous or low-water content,hygroscopic viscous carrier containing glycerine and/or propylene glycoland/or polyethylene glycol. When contacted by water, carbamide peroxidedissociates into urea and hydrogen peroxide. Associated with the slowrate of bleaching in the hygroscopic carrier, the currently availabletooth-bleaching compositions cause tooth sensitization in over 50% ofpatients. Tooth sensitivity is believed to result from the movement offluid through the dentinal tubes toward nerve endings in the tooth. Thismovement is enhanced by the carriers for the carbamide peroxide. Infact, it has been determined that glycerine, propylene glycol andpolyethylene glycol can each give rise to varying amounts of toothsensitivity following exposure of the teeth to heat, cold, overly sweetsubstances, and other causative agents.

[0007] Prolonged exposure of teeth to bleaching compositions, aspracticed at present, has a number of adverse effects in addition tothat of tooth sensitivity. These include: solubilization of calcium fromthe enamel layer at a pH less than 5.5 with associated demineralization;penetration of the intact enamel and dentin by the bleaching agents, soas to reach the pulp chamber of a vital tooth thereby risking damage topulpal tissue; and dilution of the bleaching compositions with salivawith resulting leaching from the dental tray and subsequent digestion.

[0008] The stability of existing formulations of hydrogenperoxide-containing tooth-bleaching compositions in terms of shelf-lifeas well as over the period of use in the mouth, depends, in general, onan acidic pH. The hydrogen peroxide becomes markedly less stable as thepH increases. Indeed, Frysh, et al. (Journal of Esthetic Dentistry Vol.7, No. 3, pp. 130-133, 1995) described the use of high concentration(35%) of hydrogen peroxide solutions at an initial alkaline pH, whichwas required to be formulated immediately before use and wasadministered in the form of a liquid to extracted teeth to achieve toothbleaching. Phillips and Bowles (IADR Abstract J. Dent.res 75, 1996) havedemonstrated that hydrogen peroxide penetrates the enamel of extractedteeth less readily over a 15 minute period at pH 9.0 than at pH 4.5.Carbamide peroxide compositions have been formulated at a pH of 5.0-6.5using hygroscopic carriers and maintaining a low water content. Thistype of formulation is problematic with regard to enhanced toothsensitivity. On contact with saliva, the water content of theformulation increases, causing the carbamide to disassociate into ureaand hydrogen peroxide and the pH to be decreased. In fact, theequilibrium pH of a 10% carbamide peroxide solution is approximately3.45 and a typical commercially-available tooth-bleaching gel with 10%carbamide peroxide when combined with saliva in a 1:1 weight ratio hasan initial pH of 5.6 and gradually decreases to pH 4.8 after 8 hours.

[0009] Thus, currently available tooth-bleaching compositions that relyon hydrogen peroxide as oxidizing agents, all release hydrogen peroxidefrom precursors at low pH levels despite the low rates oftooth-bleaching activity.

[0010] There is a need for a home use tooth-bleaching product that isstable, easy to use, and rapid-acting that utilizes reduced amounts ofhydrogen peroxide and is capable of administration to a patient by meansof a dental tray. There is a further need for a tooth-bleachingcomposition that may reduce hard and soft tissue irritation, toothsensitivity, and bleaching composition ingestion to further increasepatient compliance.

SUMMARY OF THE INVENTION

[0011] The invention satisfies the above needs. An embodiment of theinvention includes a tooth-bleaching composition for contacting a toothsurface in a subject that includes a hydrogen peroxide-containingcompound. Furthermore the composition includes a matrix foradministering the hydrogen peroxide-containing compound to the toothsurface. The matrix comprises a thickening agent, an agent forstabilizing the hydrogen peroxide-containing compound, a pH adjustingagent and a calcium chelating agent, wherein the pH of thetooth-bleaching composition during the bleaching process issubstantially constant within a range of pH 6.0-10.

[0012] A further embodiment of the invention includes a dosage deliveryunit for tooth bleaching, including a multi-chamber vessel wherein eachchamber is responsive to an applied pressure from an external source,such that a mixture of reagents contained within a compartment includinga hydrogen peroxide containing composition and a matrix, will be forcedto exit the compartment through a mixing baffle in response to theexternally applied pressure.

[0013] A further embodiment of the invention includes a method forbleaching teeth including preparing a composition as described above andadministering the composition to the tooth surface.

DETAILED DESCRIPTION OF THE INVENTION

[0014] The present invention comprises compositions and methods forbleaching tooth enamel in situ which allow the use of reducedconcentrations of hydrogen peroxide in tooth-bleaching compositions inorder to achieve effective tooth bleaching in a contact time of lessthan one hour.

[0015] The tooth surface is defined here and in the claims as a portionof a tooth which is directly responsible for the stained appearance ofsaid tooth. The term tooth surface generally means a tooth's acquiredpellicle, plaque, enamel, and combinations thereof.

[0016] The matrix is defined here and in the claims as the gel, paste,or liquid in which the hydrogen peroxide containing compound is placedfor administration to the subject.

[0017] The subject referred to here and in the claims is commonly ahuman subject but also includes domestic animals.

[0018] An important aspect of the present invention is the finding thatthe efficiency of the bleaching reaction in a tooth using a chemicaltooth-bleaching agent such as hydrogen peroxide can be significantlyenhanced at a pH greater than 5.5, more particularly a pH in the rangeof 6-10, for example in a range of pH of 7-10, more particularly between8.0 and 9.5, providing that the pH is maintained at a substantiallyconstant range throughout the tooth-bleaching process and a calciumchelating agent is included in the composition to prevent precipitationof calcium ions. (Table 1-4)

[0019] Suitable pH adjusting agents include, but are not limited to,sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodiumcarbonate, potassium carbonate, TRIS and triethanolamine.

[0020] Examples of calcium chelating agents include any of the calciumchelatin, agents known in the art. Examples include EDTA and its salts,citric acid and its salts, gluconic acid and its salts, alkali metalpyrophosphates and alkali metal polyphosphates. The use of citric acid,sodium acid pyrophosphate and disodium EDTA are shown in Table 1 andTable 2. The biological efficacy of sodium acid pyrophosphate is shownin Table 4. Without being bound to any particular theory, it is proposedthat calcium precipitation in the form of calcium phosphates arise inthe intercrystalline interstices of the tooth at elevated pHs and thisgives rise to a blockage of movement of the peroxide into the tooth witha resulting negative effect on tooth bleaching. Calcium chelating agentsmay prevent this precipitation of calcium ions with the associatedobserved improvement of tooth-bleaching effect.

[0021] The composition may also contain a stabilizing agent for removingfrom solution, metal ions that interfere with the action of the hydrogenperoxide. In certain formulations, a single component may act either asa calcium chelating agent or as a stabilizing agent or may serve bothfunctions.

[0022] The ability to maintain a constant pH range above 5.5 throughoutthe period of tooth bleaching coupled with the inhibition of calciumprecipitation that normally occurs at pH levels above 5.5, has resultedin a formulation that is suitable for use in the home and is capable ofachieving detectable tooth bleaching in less than 30 minutes.Furthermore, multiple treatments (each treatment lasting no longer than30 minutes) have been demonstrated to substantially whiten teeth(Example 5). In Example 5,14 treatments using the inventive formulation,were administered for twenty minutes, twice a day over seven days. Amean AE of 7.32 was observed denoting a substantial tooth-bleachingeffect compared with a AE of 4.73 using a prior art formulation for aperiod of time that was three times longer than that of the novelformulation.

[0023] According to the invention, additional agents havingtooth-bleaching effect may be used to achieve detectable tooth bleachingin less than 30 minutes. For example, sodium percarbonate has beendemonstrated to be very effective at tooth bleaching when maintained ata pH that is greater than 5.5, more preferably in the range of 7-10,more particularly 8-9.5 that includes a calcium chelating agent. Thiscomposition differs from carbamide peroxide in that there is noacidification of that solution that results upon its dissociation.Consequently, the reagent may be maintained at a constant elevated pHfor an extended period of time without the necessity for addingbuffering reagents beyond that naturally supplied in the saliva. Unlikecarbamide peroxide, however, the percarbonate is prepared in aformulation that does not include glycerine and is only slowly permeatedby water whereupon hydrogen peroxide is released. For his reason, it maybe desirable, but is not essential, to prepare the percarbonate in atwo-component composition, the two components being mixed before use soas to accelerate the tooth-bleaching effect (Examples 1 and 2).Formulations containing two components may be applied to the dental trayby squeezing a tube in much the same way as a single component. Themixing of the two components can be readily achieved using amulti-component tube containing a baffle, otherwise known in the art asa static mixer such that on squeezing the tube, material from each ofthe compartments is forced through the static mixer and are mixedtogether before emerging from a single exit in the tube.

[0024] The present invention has important health benefits that followfrom shorter contact times of the tooth with hydrogen peroxide as wellas the need for lower concentrations of peroxide to achieve a desiredtooth-bleaching effect.

EXAMPLE 1 Composition of a Stable Tooth-Bleaching Formulation Suitablefor Use in a One Component System

[0025] The formulations below utilized ultrapure components to avoiddestabilization caused by metal ion contaminants. The chelating agentused here is one of disodium EDTA (1C), citric acid (1B), and sodiumacid pyrophosphate (1F). The pH is modified using one of sodiumhydroxide monohydrate (1A, 1B, 1C), ammonium hydroxide (1F,1G),Tris(hydroxymethyl) aminomethane (1D), and triethanolamine (1E).Carbopol is a high molecular weight crosslinked polyacrylic acidthickening agent. Hydrogen peroxide is used as the oxidizino agent.TABLE 1 Example 1 A B C D E F G Ingredient WEIGHT PERCENT DistilledWater 86.41 86.21 86.31 72.80 79.52 86.50 73.81 1-Hydroxyethylidene-1,1-0.02 0.02 0.02 0.03 0.02 0.30 0.40 diphosphonic acid Sodium stannatetrihydrate 0.02 0.02 0.02 0.03 0.02 0.05 0.05 Citric acid — 0.20 — — — —0.10 Calcium disodium EDTA — — 0.10 — — — — Sodium acid pyrophosphate —— — — — 0.30 — Hydrogen Peroxide 35% 10.30 10.30 10.30 17.14 17.14 8.6017.14 Carbopol 974P 2.50 2.50 2.50 5.00 — 3.00 5.00 (B F Goodrich)Carbopol 934P — — — — 2.00 — — (B F Goodrich) Sodium Hydroxide to pH 7.0to pH 7.0 to pH 7.0 — — — — Monohydrate Ammonium hydroxide 28% — — — — —to pH 6.5 to pH 8.5 Tris(hydroxymethyl) — — — to pH 8.0 — — —aminomethane Triethanolamine — — — — to pH 6.0 — — Total 100 100 100 100100 100 100 pH @ 25 deg. C. 7.0 7.0 7.0 8.0 6.0 6.5 8.5

[0026] The above formulations were prepared by dissolving thestabilizers 1-hydroxyethylidene-1,1-diphosphonic acid and the sodiumstannate trihydrate in the distilled water using a Kynar-coatedpropeller-type agitator (reserving enough water, if necessary, todissolve the neutralizer in the final step). The hydrogen peroxide wasthen added slowly to this mixture. The Carbopol 974P was then added tothe distilled water/stabilizer/hydrogen peroxide mixture slowly while avortex was formed with the agitator blade. This dispersion was thenplaced in a Kynar-coated vacuum double planetary mixer to which the pHadjusting agent was added slowly to affect neutralization of theCarbopol 974P and to adjust the final composition pH. The resultingcomposition was a transparent, viscous gel and was packaged infoil/plastic laminate tubes having a polyethylene product contact liner.

EXAMPLE 2 A Two Component Alkaline Tooth-Bleaching Formulation

[0027] A hydrogen peroxide-releasing composition was formulated whichutilized sodium percarbonate in an anhydrous gel, and was designed to becombined with a separate aqueous gel prior to use in order to dissolvethe sodium percarbonate to form hydrogen peroxide and sodium carbonate.The pH of this composition, shown in Table 2, when combined in a volumeratio of 1 to 1, was 9.0. The chelating agents used here are EDTA andsodium acid pyrophosphate. TABLE 2 EXAMPLE 2 PART A PART B INGREDIENTWEIGHT PERCENT Distilled Water — 95.20  Polyethylene glycol 400 83.00 —Sodium percarbonate (powder) 12.00 — EDTA — 0.20 Sodium acidpyrophosphate — 0.30 Carbopol 974P (EF Goodrich)  2.50 4.00 SodiumHydroxide Monohydrate — to pH 7.0 Tris(hydroxymethyl)aminomethane  2.50— Total 100    100   

[0028] The above composition parts were prepared as follows:

[0029] Part A

[0030] The Carbopol was dispersed in the polyethylene glycol using apropeller-type agitator with Kynar-coated product contact surfaces. Theresulting dispersion was added to a Kynar-coated vacuum double planetarymixer (as in Example 1) and neutralized with thetris(hydroxymethyl)aminomethane under low shear mixing. To the resultantneutralized Carbopol gel, sodium percarbonate was added and disperseduntil the composition was a homogenous white paste.

[0031] Part B

[0032] The Carbopol was added to the water (in which the EDTA and sodiumacid pyrophosphate had already been dissolved) and agitated as above.The resulting dispersion was transferred to the Kynar-coated vacuumdouble planetary mixer and neutralized with the sodium hydroxidemonohydrate under low shear mixing. The final gel was clear and viscous,with a pH of around 7.0.

EXAMPLE 3 Preparation of a Tooth-Bleaching Formulation Having Acidic pH

[0033] In order to demonstrate the superior ability of the inventivehydrogen peroxide gel composition of Examples 1 and 2 to bleach teeth, acomposition was prepared which was similar to that of Example 1E, exceptthat the pH was adjusted to 4.5. TABLE 3 INGREDIENT PERCENT Distilledwater 79.82  1-Hydroxyethylidene-1,1-diphosphonic acid 0.02 Sodiumstannate trihydrate 0.02 Carbopol 974P 2.00 Hydrogen Peroxide 35% 17.14 Triethanolamine 1.00 TOTAL 100.00 

[0034] The formulation was prepared as in Example 1, resulting in atransparent, viscous gel with a pH of approximately 4.5. The formulationis similar to 1E, the difference lying in the pH of the composition.

EXAMPLE 4 Assay to Determine Tooth Bleaching

[0035] Bovine incisors, which had been imbedded in an acrylic matrixsuch that the buccal surfaces presented themselves on the top surface,were stained in a manner to duplicate the tooth staining observed invivo by humans (alternately exposed to air and a staining broth at 37degrees C. containing typticase soy broth, tea, coffee, mucin, FeCl₃,and Sarcina lutea, for a period of about four days). Each stained bovineincisor was numbered and measured for degree of staining (color by theCIELAB protocol) with a Minolta 5031 Spectrophotometer (3 mm aperture, 8exposure averaging, outliers discarded). Incisors were covered withdifferent tooth-bleaching compositions in the tables above, in additionto a commercially available carbamide peroxide composition (Opalescence10% Carbamide Peroxide Gel, Ultradent, South Jordan, Utah). All gelswere kept in contact with the incisor surface for exactly 15 minutes,whereupon the tooth was rinsed clean of any gel residue with distilledwater and swabbed with saliva. The degree of stain removal wasthereafter immediately determined by measuring the incisor surface, asabove, for color, and the change in tooth color recorded below as ΔE.Absolute color change is defined as the square root of the sum of thesquares of all color components (L, a, and b).

{square root}[(ΔL)²+(Δa)²+(Δb)² ]=ΔE TABLE 4 Product/ pH Initial ColorFinal Color Tooth # Example (neat) L a b L a b ΔE 1 Opalescence 6.541.79 3.17 11.78 44.29 2.96 11.70 2.51 2 Example 3 4.5 39.84 4.99 12.0043.96 4.47 10.94 4.29 3 1E 6.0 40.44 4.41 9.53 46.32 3.48 7.54 6.27 4 1A7.0 36.02 3.84 10.10 42.57 2.59 8.28 6.91 5 1B 7.0 38.81 3.98 11.3845.92 2.38 8.81 7.73 6 1C 7.0 36.90 4.05 12.61 44.11 2.45 10.53 7.67 71D 8.0 41.55 3.67 10.51 49.77 1.26 7.82 8.98 8 1F 6.5 38.55 5.01 10.8744.78 3.67 9.50 6.52 9 1G 8.5 40.26 4.59 9.93 48.28 3.13 7.97 8.38 10 Example 2 9.0 36.49 4.00 12.64 44.93 2.20 10.63 8.78

[0036] This table shows the effect of pH on tooth bleaching. As shownfor tooth #2 treated with the formulation of Example 3 and tooth #3treated with the formulation

[0037] The results of direct tooth surface (upper left central incisor)color measurements, both before and after treatment (as in Example 5above), are recorded in the Table 5 below. TABLE 5 Patient Product/Treatment Initial Color Final Color # Example Time (minutes) L a b L a bΔE 1 1B 280 53.76 4.65 11.65 60.34 0.97 8.80 8.06 2 1B 280 49.42 2.979.48 56.99 0.46 7.38 8.25 3 1B 280 51.26 2.33 8.25 55.63 0.87 4.99 5.654 Opalescence 840 52.78 1.75 6.14 57.26 1.42 2.10 6.04 5 Opalescence 84056.35 1.79 5.21 59.13 0.65 2.44 4.09 6 Opalescence 840 55.71 2.72 7.1058.60 1.09 4.75 4.07

[0038] The average ΔE for the Example IB group was 7.32, whereas theaverage ΔE for the Opalescence group was 4.73. The present inventivecompositions are thus shown to offer a substantially improved degree oftooth bleaching in a shorter exposure time than a prior art composition.

I claim:
 1. A tooth-bleaching composition for contacting a tooth surfacein a subject, the composition comprising: a first formulation having ahydrogen peroxide-containing compound; and a separate second formulationhaving a thickening agent, a pH adjusting agent, and less than 0.5% byweight, based on the weight of the composition, of a calcium chelatingagent; wherein the first and second formulations remain separate and aremixed with one another, prior to use, to form the composition.
 2. Atooth-bleaching composition according to claim 1, wherein the hydrogenperoxide-containing compound is a percarbonate salt.
 3. Atooth-bleaching composition according to claim 2, wherein thepercarbonate salt is selected from the group consisting of sodium andpotassium percarbonate.
 4. A tooth-bleaching composition according toclaim 1, wherein the hydrogen peroxide-containing compound is hydrogenperoxide.
 5. A tooth-bleaching composition according to claim 4, whereinthe concentration of hydrogen peroxide in the composition is less than15% by weight of the composition.
 6. A tooth-bleaching compositionaccording to claim 1, wherein the composition has a pH in a range offrom about 6.0 to about 10.0.
 7. A tooth-bleaching composition accordingto claim 6, wherein the composition has a pH in a range of from about8.0 to about 9.5.
 8. A tooth-bleaching composition according to claim 1,wherein the calcium chelating agent is selected from the groupconsisting of EDTA and its salts, citric acid and its salts, gluconicacid and its salts, alkali metal pyrophosphates and alkali metalpolyphosphates.
 9. A tooth-bleaching composition according to claim 8,wherein the calcium chelating agent further acts as a stabilizing agentfor the peroxide-containing compound.
 10. A tooth-bleaching compositionaccording to claim 1, wherein wherein the calcium chelating agent is1-hydroxyethylidene-1,1-diphosphonic acid.
 11. A tooth-bleachingcomposition according to claim 1, wherein the composition is capable ofa detectable tooth-bleaching effect within 30 minutes.
 12. Atooth-bleaching composition according to claim 1, wherein each of thefirst and second formulations are formulated for storage within achamber of a multi-chamber vessel, such that in the presence of anexternally applied pressure, each of the formulations is forced to exitits respective chamber through a mixing baffle to form the composition.